Quantitative multi-modal functional MRI with blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR)

A magnetic resonance imaging (MRI) method is described that allows interleaved measurements of transverse (R(2)(*) and R(2)) and longitudinal (R(1)) relaxation rates of tissue water in conjunction with spin labeling. The image-contrasts are intrinsically blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) weighted, but each contrast is made quantitative by two echo time (TE) and inversion recovery time (TIR) acquisitions with gradient echo (GE) and spin echo (SE) weighted echo-planar imaging (EPI). The EPI data were acquired at 7 Tesla with nominal spatial resolution of 430 x 430 x 1000 microm(3) in rat brain in vivo. The method is termed as blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR) and allows acquisition of R(2)(*), R(2), and CBF maps in an interleaved manner within approximately 12 minute. The basic theory of the method, associated experimental/systematic errors, and temporal restrictions are discussed. The method is validated by comparison of multi-modal maps obtained by BOLDED AFFAIR (i.e., two TE and TIR values with GE and SE sequences) and conventional approach (i.e., multiple TE and TIR values with GE and SE sequences) during varied levels of whole brain activity. Preliminary functional data from a rat forepaw stimulation model demonstrate the feasibility of this method for functional MRI (fMRI) studies. It is expected that with appropriate precautions this method in conjunction with contrast agent-based MRI has great potential for quantitative fMRI studies of mammalian cortex.     

Assessment of data acquisition parameters,and analysis techniques for noise reduction in spinal cord fMRI data

Purpose

The purpose of this work is to characterize the noise in spinal cord functional MRI, assess current methods aimed at reducing noise, and optimize imaging parameters.

Methods

Functional MRI data were acquired at multiple echo times and the contrast-to-noise ratio (CNR) was calculated. Independently, the repetition time was systematically varied with and without parallel imaging, to maximize BOLD sensitivity and minimize type I errors. Noise in the images was characterized by examining the frequency spectrum, and investigating whether autocorrelations exist. The efficacy of several physiological noise reduction methods in both null (no stimuli) and task (thermal pain paradigm) data was also assessed. Finally, our previous normalization methods were extended.

Results

The echo time with the highest functional CNR at 3 Tesla is at roughly 75 msec. Parallel imaging reduced the variance and the presence of autocorrelations, however the BOLD response in task data was more robust in data acquired without parallel imaging. Model-free based approaches further increased the detection of active voxels in the task data. Finally, inter-subject registration was improved.

Conclusions

Results from this study provide a rigorous characterization of the properties of the noise and assessment of data acquisition and analysis methods for spinal cord and brainstem fMRI.     

Effects of static and radiofrequency magnetic field inhomogeneity in ultra-high field magnetic resonance imaging

To characterize the severe static (B(0)) and radiofrequency (B(1)) magnetic field inhomogeneity in ultra-high field (> or =7 T) magnetic resonance imaging, gradient echo (GE) and spin echo (SE) images of in vivo and postmortem human brains were acquired. The B(0) and B(1) inhomogeneity were experimentally mapped and/or numerically simulated, and correlated with the image artifacts. Whereas B(0) inhomogeneity affects predominantly GE images near air/tissue interfaces, B(1) inhomogeneity affects SE images more severely and shows non-intuitive patterns. Mapping of the B(0) and B(1) inhomogeneity is important in characterizing image artifacts. This will help develop better B(0) and B(1) inhomogeneity correction methods.     

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically “run” and “frozen” during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T₂-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.     

Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.     

STrategically Acquired Gradient Echo (STAGE) imaging,part III: Technical advances and clinical applications of a rapid multi-contrast multi-parametric brain imaging method

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images.     

Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup

Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75×150×300 μm³ and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and −2.4%, respectively. Finally, the first high-resolution (500 μm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.     

High spatial resolution BOLD fMRI using simultaneous multislice excitation with echo-shifting gradient echo at 7 Tesla

We introduce an accelerated gradient echo (GRE) sequence combining simultaneous multislice excitation (SMS) with echo-shifting technique for high spatial resolution blood oxygen level dependent (BOLD) functional MRI (fMRI). The simulation was conducted to optimize scan parameters. To validate the feasibility of the proposed technique, the visual and motor task experiments were performed at 7.0 Tesla (T). The single-shot EPI sequence was also applied in comparison with the proposed technique. The simulation results showed that an optimized flip angle of 9° provided maximal BOLD contrast for our scanning scheme, allowing low power deposition and SMS acceleration factor of 5. Additionally, parallel acquisition imaging with acceleration factor of 2 was utilized, which allowed a total acceleration factor of 10 in volunteer study. The experiment results showed that geometric distortion-free BOLD images with voxel size of 1.0 × 1.0 × 2.5 mm³ were obtained. Significant brain activation was identified in both visual and motor task experiments, which were in accordance with previous investigations. The proposed technique has potential for high spatial resolution fMRI at ultra-high field because of its sufficient BOLD sensitivity as well as improved acquisition speed over conventional GRE-based techniques.     

Laminar specificity in monkey V1 using high-resolution SE-fMRI

The lamination of mammalian neocortex is widely used as reference for describing a wide range of anatomical and physiological data. Its value lies in the observation that in all examined species, cortical afferents, intrinsic cells and projection neurons organize themselves with respect to the laminae. The comprehension of the computations, carried out by the neocortical microcircuits, critically relies on the study of the interlaminar connectivity patterns and the intralaminar physiological processes in vivo. High-resolution functional neuroimaging, enabling the visualization of activity in individual cortical laminae or columns, may greatly contribute in such studies. Yet, the BOLD effect, as measured with the commonly used GE-EPI, contains contributions from both macroscopic venous blood vessels and capillaries. The low density of the cortical veins limits the effective spatial specificity of the fMRI signal and yields maps that are weighted toward the macrovasculature, which thus can be significantly different from the actual site of increased neuronal activity. Spin-echo (SE) sequences yielding apparent T2-weighted BOLD images have been shown to improve spatial specificity by increasing the sensitivity of the signal to spins of the parenchyma, particularly at high magnetic fields. Here we used SE-fMRI at 4.7 T to examine the specificity and resolution of functional maps obtained by stimulating the primary visual cortex of monkeys. Cortical layers could be clearly visualized, and functional activity was predominantly localized in cortical layer IV/Duvernoy layer 3. The choice of sequence parameters influences the fMRI signal, as the SE-EPI is by nature sensitive to T2* in addition to its T2 dependency. Using parameters that limit T2* effects yielded higher specificity and better visualization of the cortical laminae. Because the demands of high-spatial resolution using SE severely decreases temporal resolution, we used a stimulus protocol that allows sampling at higher effective temporal resolution. This way, it was possible to acquire high-spatial and high-temporal resolution SE-fMRI data.     

Differentiation of hepatic cavernous hemangioma from metastases by rare sequence MR imaging.

In this study, in order to differentiate cavernous hemangioma and hepatic metastases, rapid acquisition relaxation enhanced (RARE) sequence was used. First, in vivo measurements of T1, T2 relaxation times and proton density were obtained using T1, T2 calculation protocol (TOMIKON S50, 0.5T) and multipoint techniques. These measurements were made from regions of interest placed over the liver, spleen (because of similarity of relaxation time values between hepatic metastases and spleen) and cavernous hemangioma (HCH). Based on these intrinsic parameters, T2 curves signal intensity of three different tissues were constructed. At TE = 500 ms, the signal intensity of the liver and spleen has been near zero whereas in HCH, the signal intensity remained. As RARE sequence is very similar to spin echo (SE), by replacing effective TE(ETE) = 500 ms in the RARE equation, two dimensional contrast-to-noise ratio (CNR) contour plots were constructed demonstrating signal intensity contrast between liver-spleen, liver-Hemangioma for two different scan times (3 min, 7.5 s) and pulse timing. Then, optimal RARE factor and inter echo times were obtained in order to have maximum CNR between liver-Hemangioma and minimum CNR between liver-spleen. These optimal parameters were performed on ten normal and five persons with known HCH. Images showed that in both scan times (3 min, 7.5 s); the liver and spleen were suppressed whereas the HCH was enhanced. The image quality in the scan time of 3 min was better than the scan time of 7.5 s. Moreover, in this study, two different sequences were compared: i) Multi-slice single echo (MSSE) for T1 weighted image ii) RARE (ETE = 80 ms) for T2-weighted image. This comparison was done to show maximum CNR between liver-spleen (metastases) and to choose a better sequence for detecting metastases. CNR in the RARE sequence was more than in the MSSE sequence.     

The effects of single-trial averaging on the temporal resolution of functional MRI

Computer simulations and event-related functional MRI (ER-fMRI) experiments were performed to investigate the effects of single-trial averaging and the corresponding contrast-to-noise ratio (CNR) on the minimal resolvable hemodynamic timing difference between brain areas. Three ER-fMRI sessions with temporally delayed (250, 500 and 1,000 ms) visual stimulations between two hemifields, each with 70 repeated single trials, were examined on two subjects. From the computer simulation, the temporal resolution improved as the CNR increased, which reached 500 and 100 ms for CNRs of 1.55 and 6.44, respectively. In the ER-fMRI experiments, the measured CNR increased as more single trials were averaged. The detectability of temporal differences was positively correlated (P<.05) with the CNR in all sessions for one subject but only in the 1,000-ms session for the other subject. Temporal resolution of 1,000 ms was achieved when more than 10 trials were averaged. The 500- and 250-ms delays might be differentiable when more than 20 trials were averaged, but the results were subject-dependent. This study demonstrated that the CNR could be significantly improved by single-trial averaging, which led to an improved temporal resolution of ER-fMRI. Temporal resolution in the range of hundreds of milliseconds was subject-dependent, which might be attributed to the intrinsic spatial variations in the timing of the blood oxygenation level-dependent (BOLD) response.     

Influence of baseline hematocrit on between-subject BOLD signal change using gradient echo and asymmetric spin echo EPI

The dependence of BOLD signal change (BSC) on baseline hematocrit is in the process of being characterized, primarily using conventional Gradient Echo (GE) echo planar imaging (EPI). We describe the first empiric exploration of this relationship using, in addition to GE, Spin Echo (SE) and two Asymmetric Spin Echo EPI sequences (ASE10 and ASE20), which are less susceptible to large vessel noise. Motor cortex BSC was measured (N = 17) and regressed against hematocrit and hemoglobin concentration using linear and non-linear functions. GE measurements of BSC yielded a positive linear relationship (r(2) = 0.240, p = 0.0459) whereas a positive non-linear relationship was observed using ASE10 (r(2) = 0.571, p = 0.0146). Results suggest that between-subjects BSC is significantly dependent on baseline hematocrit. The nature of dependence, and implications for quantitative studies vary with the vessel size selectivity of the imaging sequence, and with the effect of hematocrit on blood viscosity in the imaged vessels.     

Sensitivity limitations of high-resolution perfusion-based human fMRI at 7 Tesla

The study of the brain's functional organization at laminar and columnar level of the cortex with blood oxygenation-level dependent (BOLD) functional MRI (fMRI) is affected by the contribution of large veins downstream from the microvascular response to brain activity. Blood volume- and especially perfusion-based techniques may reduce this problem because of their reduced sensitivity to venous effects, but may not allow the same spatial resolution because of smaller signal changes associated with brain activity. Here we investigated the practical resolution limits of perfusion-weighted fMRI in human visual stimulation experiments. For this purpose, we used a highly sensitive, single-shot perfusion labeling (SSPL) technique at 7 T and compared sensitivity to detect visual activation at low (2 mm, n = 10) and high (1 mm, n = 8) nominal isotropic spatial, and 3 s temporal, resolution with BOLD in 5½-minute-long experiments. Despite the smaller absolute signal change with activation, 2 mm resolution SSPL yielded comparable sensitivity to BOLD. This was attributed to a superior suppression of physiological noise with SSPL. However, at 1 mm nominal resolution, SSPL sensitivity fell on average at least 42% below that of BOLD, and detection of visual activation was compromised. This is explained by the fact that at high resolution, with both techniques, typically thermal noise rather than physiological noise dominates sensitivity. The observed sensitivity loss implies that to perform 1-mm resolution, perfusion weighted fMRI with a robustness similar to BOLD, scan times that are almost 3 times longer than the comparable BOLD experiment are required. This is in line with or slightly better than previous comparisons between perfusion-weighted fMRI and BOLD. The lower sensitivity has to be weighed against the spatial fidelity advantages of high-resolution perfusion-weighted fMRI.     

Signal fluctuations in fMRI data acquired with 2D-EPI and 3D-EPI at 7 Tesla

Segmented three-dimensional echo planar imaging (3D-EPI) provides higher image signal-to-noise ratio (SNR) than standard single-shot two-dimensional echo planar imaging (2D-EPI), but is more sensitive to physiological noise. The aim of this study was to compare physiological noise removal efficiency in single-shot 2D-EPI and segmented 3D-EPI acquired at 7 Tesla. Two approaches were investigated based either on physiological regressors (PR) derived from cardiac and respiratory phases, or on principal component analysis (PCA) using additional resting-state data. Results show that, prior to physiological noise removal, 2D-EPI data had higher temporal SNR (tSNR), while spatial SNR was higher in 3D-EPI. Blood oxygen level dependent (BOLD) sensitivity was similar for both methods. The PR-based approach allowed characterization of relative contributions from different noise sources, confirming significant increases in physiological noise from 2D to 3D prior to correction. Both physiological noise removal approaches produced significant increases in tSNR and BOLD sensitivity, and these increases were larger for 3D-EPI, resulting in higher BOLD sensitivity in the 3D-EPI than in the 2D-EPI data. The PCA-based approach was the most effective correction method, yielding higher tSNR values for 3D-EPI than for 2D-EPI postcorrection.     

Combination of BOLD-fMRI and VEP recordings for spin-echo MRI detection of primary magnetic effects caused by neuronal currents

In the present paper, for the first time, the feasibility to detect primary magnetic field changes caused by neuronal activity in vivo by spin-echo (SE) magnetic resonance imaging (MRI) is investigated. The detection of effects more directly linked to brain activity than secondary hemodynamic–metabolic changes would enable the study of brain function with improved specificity. However, the detection of neuronal currents by MRI is hampered by such accompanying hemodynamic changes. Therefore, SE image acquisition, rather than gradient-echo (GE) image acquisition, was preferred in the present work since the detection of primary neuronal and not blood oxygenation level-dependent (BOLD)-related effects may be facilitated by this approach. First of all, a precise spatiotemporal synchronization of image acquisition with the neuronal event had to be performed to avoid refocusing of the dephasing phenomenon during the course of the SE sequence. At this aim, we propose the combined use of visual evoked potential (VEP) recordings and BOLD-fMRI measurements prior to SE MRI scanning. Moreover, we exemplify by theory and experimentation how the control of artefactual signal changes due to BOLD and movement effects may be further improved by the experimental design. Finally, results from a pilot study using the proposed combination of VEP recordings and MRI techniques are reported, suggesting the feasibility of this method.     

Dual-echo breathhold T(2)-weighted fast spin echo MR imaging of liver lesions

The purpose of this study was to develop a multi-shot dual-echo breathhold fast spin echo technique (DFSE) and compare it with conventional spin echo (T2SE) for T(2)-weighted MR imaging of liver lesions. The DFSE acquisition (EffTE1/EffTE2/TR = 66/143/2100 ms) imaged 5 sections per 17 s breathhold. T2SE imaging (TE1/TE2/TR = 60/120/2500 ms) required 16:55 (min:s) for 14 sections. Both techniques used a receive-only phased-array abdominal multicoil and provided 192 x 256 effective resolution. The results showed first and second echo relative DFSE/T2SE contrast values for 27 representative lesions (15 consecutive patients) were 1.08 +/- 0.05 and 1.16 +/- 0.09 (mean +/- STD mean), respectively. Corresponding CNR values were 1.12 +/- 0.09 and 0.97 +/- 0.12. Overall DFSE was comparable-to-superior to T2SE for lesion sizing and image artifact. DFSE lesion detection was inferior to T2SE's in several patient studies because of decreased conspicuity of lesions located near multicoil edges and because of poor breathhold-to-breathhold reproducibility and lack of breathholding. However both DFSE (and T2SE) provided lesion detection rated to be of diagnostic quality for all patient studies. In conclusion, we found that DFSE provides diagnostically useful dual-echo T(2)-weighted MR liver images in a greatly decreased acquisition time.     

Characterization of high-resolution Gradient Echo and Spin Echo EPI for fMRI in the human visual cortex at 7 T

The increased signal-to-noise ratio (SNR) offered by functional Magnetic Resonance Imaging (fMRI) at 7T allows the acquisition of functional data at sub-millimetric spatial resolutions. However, simply reducing partial volume effects is not sufficient to precisely localize task-induced activation due to the indirect mechanisms that relate brain function and the changes in the measured signal.In this work T2* and T2 weighted Echo Planar Imaging (EPI) schemes based on Gradient Recalled Echo (GRE) and Spin Echo (SE) were evaluated in terms of temporal SNR, percent signal change, contrast to noise ratio (CNR), activation volume, and sensitivity and specificity to gray matter. Datasets were acquired during visual stimulation at in-plane resolutions ranging between 1.5 × 1.5 mm² and 0.75 × 0.75 mm² targeting the early visual cortex.While similar activation foci were obtained in all acquisitions, at in-plane resolutions of 1.0 × 1.0 mm² and larger voxel sizes the T2 weighted contrast of SE-EPI allowed the identification of the activation site with better spatial accuracy. However, at sub-millimetric resolutions the decrease in temporal SNR significantly hampered the sensitivity and the extent of the activation site. On the other hand, high resolution T2* weighted data collected with GRE-EPI provided higher CNR and sensitivity, benefiting from the decreased physiological and partial volume effects. However, spurious activations originating from regions of blood drainage were still present in GRE data, and simple thresholding techniques were found to be inadequate for the removal of such contributions. The combination of 2-class and 3-class automated segmentations, performed directly in EPI space, allowed the selection of active voxels in gray matter. This approach could enable GRE-EPI to accurately map functional activity with satisfactory CNR and specificity to the true site of activation.     

Development of visually evoked cortical activity in infant macaque monkeys studied longitudinally with fMRI

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development.     

esfMRI of the upper STS: further evidence for the lack of electrically induced polysynaptic propagation of activity in the neocortex

Combining electrical stimulation with fMRI (esfMRI) has proven to be an important tool to study the global effects of electrical stimulation on neural networks in the brain. Here we extend our previous studies to stimulating the upper superior temporal sulcus (STS) in the anesthetized monkey. Our results show that stimulating area V5/MT and surrounding areas leads to positive BOLD responses in the majority of cortical areas known to receive direct/monosynaptic connections from the stimulation site. We confirm our previous results from stimulating primary visual cortex that the propagation of electrically induced activity is limited in its transsynaptic propagation to the first synapse also for extrastriate areas.     

Integration of EEG source imaging and fMRI during continuous viewing of natural movies

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an estimate of the current density at every time point. We then carried out a correlation between the time series of visual contrast changes in the movie with that of EEG voxels. We found the most significant correlations in visual area V1, just as seen in previous fMRI studies (Bartels A, Zeki, S, Logothetis NK. Natural vision reveals regional specialization to local motion and to contrast-invariant, global flow in the human brain. Cereb Cortex 2008;18(3):705–717), but on the time scale of milliseconds rather than of seconds. To obtain an estimate of how the EEG signal relates to the BOLD signal, we calculated the IRF between the BOLD signal and the estimated current density in area V1. We found that this IRF was very similar to that observed using combined intracortical recordings and fMRI experiments in nonhuman primates. Taken together, these findings open a new approach to noninvasive mapping of the brain. It allows, firstly, the localization of feature-selective brain areas during natural viewing conditions with the temporal resolution of EEG. Secondly, it provides a tool to assess EEG/BOLD transfer functions during processing of more natural stimuli. This is especially useful in combined EEG/fMRI experiments, where one can now potentially study neural-hemodynamic relationships across the whole brain volume in a noninvasive manner.